Free radicals are hotspot in the research of life sciences. In 1956, Harman of the United States introduced the concept of free radicals in radiation chemistry into the field of biology and proposed the famous free radial theology. Reactive oxygen species (ROS) is the most common free radical in the body. The free radicals in the human body are mainly oxygen free radicals. Excessive reactive oxygen species in the body can cause lipid peroxidation, change biofilm structures and functions, cause protein denaturation, cross-linking, enzyme inactivation and so on. Reactive oxygen species is closely related to the occurrence and development of myocardial shock, radiation injury, atherosclerosis, immune system defects and other diseases. Excessive free radicals induce oxidation reaction in organism, damage the body's tissues and cells, and then lead to aging, so Harman proposed the famous free radical theory of aging. Oxidative stress leads to oxidative damage of biomolecules, causing endogenous damage associated molecular patterns (DAMPs) to produce and release cytokines. Cytokines can activate signaling pathways downstream of pattern recognition receptors (PRRs) such as nuclear factor κB (NF-κB), JAK, STAT and MAPK and so on, leading to increased cytokines and chemokines release, recruitment and activation of more inflammation cells, causing systemic chronic inflammatory response. Based on the tight relationship between oxidative stress and inflammation, aging, De la Fuente et al. proposed the oxidation-inflammatory aging theory and thought that oxidative stress leads to inflammatory aging.
Superoxide dismutase is widely found in various organisms, an indispensable, important oxygen free radical scavenger in body, and plays an important role in the biological defense of oxidative damage. Depending on the combined metal ions, SOD can be divided into four categories: Cu/Zn-SOD, Fe-SOD, Mn-SOD and Ni-SOD. Studies have shown that SOD can remove oxygen free radicals effectively, treat a variety of inflammation, and also play an important role in the prevention and treatment of radiation damage. Wherein, the Mn-SOD is the most stable, with the minimal toxicity.
In the oxidized and phosphorylated electron transport system of mitochondria, the molecule O2 is the last receptor. In normal circumstances O2 receives four electrons and turns into H2O. If part of the electrons are transferred, a highly active oxygen free radical (ROS) is formed, and the oxygen free radical attacks lipid membrane, protein, DNA, causing neurodegeneration, aging, cancer, pulmonary fibrosis, vascular disease. ROS is also an important factor in the induction of inflammatory response. Inflammation is the body's defensive response to infection source, trauma, or tissue ischemia. Abnormal inflammatory response causes a variety of diseases. The most common pathological features of inflammation are the migration, aggregation and infiltration of leukocytes (neutrophils and macrophages). The research of the location and number of neutrophils is the most common method of studying inflammation. Many experiments have shown that antioxidant enzymes are the main regulator of inflammatory response. Mn-SOD in mitochondria is the first enzyme to remove oxygen free radicals, and its activity relates to the scavenging rate of free radical and the repair efficiency of inflammation.
Mammalian Mn-SOD is located in the mitochondria, and its function is to control the mitochondrial O2− level, to avoid the damage of oxygen free radical to mitochondria. Studies on the function of Mn-SOD in vivo have shown that Mn-SOD is closely related to inflammatory response and cell senescence. The mitochondria in most of the mice lacking the gene have serious damage. After the gene is knocked out, the mice often die in the fetal phase, while supplementation with Mn-SOD can prolong the survival time. Mn-SOD may become a new anti-inflammatory drug.
Environmental pollution, psychological stress, addiction to tobacco and alcohol and other bad habits will lead to abnormal metabolism in the body. A large number of oxygen free radicals accumulation leads to depression, fatigue, reduced immunity, causing a sub-health state for a long time. If one can supplement adequate amount of SOD, these sub-health symptoms will be improved. Therefore, SOD can be used for health care products or as food additives. In addition, Mn-SOD also has a role in the anti-aging, prevention of skin pigmentation, which can also be added and applied in cosmetics.
Although the current basic research has proved the action mode of SOD and its effect, but SOD is still difficult to be practically applied, and cannot achieve the desired therapeutic efficiency. This is mainly caused by the following factors: firstly, due to the procedure of drug preparation, cosmetics and food processing usually involves the steps of sterilization, heating extraction and so on, while the characteristics of ordinary SOD are poor stability, high temperature intolerant, long-term storage intolerant, which seriously constrain its industrial applications; secondly, SOD is a biological macromolecular, the transdermal absorption amount is limited, thus its efficacy may be limited; finally, both oral drugs and food are digested and absorbed through the digestive tract, SOD as a kind of protein is often digested and degraded by the protease in gastric juice and intestinal fluid, which cannot play its due effect. The European Food Safety Authority (EFSA) argues that more evidences are needed for the role of SOD in promoting health (EFSA Journal 2010; 8 (10): 1753).
Although many researchers have also explored a number of studies, such as the production of high temperature resistant SOD using genetic engineering methods in order to overcome these deficiencies. So far, the following technical problems have not been overcome in the prior art: 1) recombinant SOD is insufficient in resistance to acid and alkali; 2) the produced SOD is easily degraded by the pepsin and trypsin in the digestive tract and losses activity.
Therefore, the deficiency of the prior SOD in resistance to high temperature, acid and alkali, pepsin and trypsin degradation greatly limits the application of SOD in the fields of cosmetics, food and medicine. It is urgent to develop a new superoxide dismutase that is resistant to high temperature, acid and alkali, pepsin and trypsin degradation simultaneously.